Glucose-dependent insulinotropic peptide (GIP) and Glucagon-like Peptide-1 (GLP-1) are incretins which regulate the amount of insulin that is secreted after eating (Kim and Egan, Pharm Rev 60:470-512 (2008)). In specific, GIP exerts glucose-dependent stimulatory effects on insulin secretion, thereby ensuring prompt insulin-mediated uptake of glucose into tissues, and GLP-1 stimulates insulin synthesis and secretion, inhibition of glucagon secretion, and inhibition of food intake. While agonist peptide analogs of both incretins have been made and tested, GLP-1 agonists have been and remain the central focus of research and development for treating of metabolic diseases, such as Type 2 diabetes. This is not surprising, since in Type 2 diabetes, GIP no longer modulates glucose-dependent insulin secretion, whereas GLP-1 retains insulinotropic activities even in Type 2 diabetetic patients. Also, research by some groups McLean et al., Am J Physiol Endocrinol Metab 296(6): E1746-1755 (epub 2007) have suggested the use of GIP antagonists and not GIP agonists for the treatment of diabetes.
When blood glucose levels begin to fall, glucagon is produced by the pancreas and the binding of this hormone to its receptor signals the liver to break down glycogen and release glucose. The actions of glucagon cause blood glucose levels to rise toward a normal level. Because glucagon exerts actions which oppose incretins, many glucagon antagonists have been made and tested for the treatment of metabolic diseases, including Type 2 diabetes.